Abstract
Background: Disentangling renal adverse drug reactions from confounders remains a major challenge to assess causality and severity in neonates, with additional limitations related to the available tools (modified Kidney Disease Improving Global Outcome, or Division of Microbiology and Infectious Diseases pediatric toxicity table). Vancomycin and amikacin are nephrotoxic while still often prescribed in neonates. We selected these compounds to assess their impact on creatinine dynamics as a sensitive tool to detect a renal impairment signal. Methods: A recently developed dynamical model that characterized serum creatinine concentrations of 217 extremely low birth weight (<1000 g, ELBW) neonates (4036 observations) was enhanced with data on vancomycin and/or amikacin exposure to identify a potential effect of antibiotic exposure by nonlinear mixed-effects modelling. Results: Seventy-seven percent of ELBW patients were exposed to either vancomycin or amikacin. Antibiotic exposure resulted in a modest increase in serum creatinine and a transient decrease in creatinine clearance. The serum creatinine increase was dependent on gestational age, illustrated by a decrease with 56% in difference in serum creatinine between a 24 or 32-week old neonate, when exposed in the 3rd week after birth. Conclusions: A previously described model was used to explore and quantify the impact of amikacin or vancomycin exposure on creatinine dynamics. Such tools serve to explore minor changes, or compare minor differences between treatment modalities.
Highlights
We reported on serum creatinine dynamics in the first 6 weeks of postnatal life in a relevant cohort with 2814 creatinine observations in 148 extreme low birth weight (
For the purpose of this project, all individual electronic medical files were searched for days exposed to vancomycin, amikacin, or both, as this is the established antibiotic regimen for suspected late onset sepsis (LOS) in the Leuven neonatal intensive care unit (NICU) [27]
77% were exposed to either vancomycin or amikacin, and 66% were simultaneously exposed to vancomycin and amikacin for at least one day (Table 3)
Summary
Disentangling renal adverse drug reactions from confounders remains a major challenge to assess causality and severity in neonates, with additional limitations related to the available tools (modified Kidney Disease Improving Global Outcome, or Division of Microbiology and Infectious Diseases pediatric toxicity table). Vancomycin and amikacin are nephrotoxic while still often prescribed in neonates We selected these compounds to assess their impact on creatinine dynamics as a sensitive tool to detect a renal impairment signal. Conclusions: A previously described model was used to explore and quantify the impact of amikacin or vancomycin exposure on creatinine dynamics Such tools serve to explore minor changes, or compare minor differences between treatment modalities
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